HDL: Fact, fiction, or function? HDL cholesterol and cardiovascular risk.

The measurement of high-density lipoprotein cholesterol is highly utilized by clinicians to help predict cardiovascular risk, but this measure is not causally associated with atherosclerotic cardiovascular disease events. The use of Mendelian randomization studies has led to a change in investigative attention from the high-density lipoprotein cholesterol concentration to its physiological functions. High-density lipoprotein plays key roles in important pathways related to the development of atherosclerotic disease including reverse cholesterol transport, oxidation and inflammation, and endothelial function as well as in other physiological systems including immune system modulation, cellular apoptosis, and endothelial progenitor cell homeostasis. The identification of dysfunctional high-density lipoprotein may better predict future cardiovascular events compared to numerical high-density lipoprotein cholesterol and aid in enhanced clinical risk stratification. The emergence of discrete physiological measurements of high-density lipoprotein, such as cholesterol efflux capacity and the high-density lipoprotein inflammatory index, may provide an opportunity for clinical application in the future. However, the validity of these measurements and their commercial availability remain barriers to a realistic transition to clinical medicine.

Myocardial Ischemia and Mobilization of Circulating Progenitor Cells.

BackgroundThe response of progenitor cells (PCs) to transient myocardial ischemia in patients with coronary artery disease remains unknown. We aimed to investigate the PC response to exercise-induced myocardial ischemia (ExMI) and compare it to flow mismatch during pharmacological stress testing. Methods and ResultsA total of 356 patients with stable coronary artery disease underwent 99mTc-sestamibi myocardial perfusion imaging during exercise (69%) or pharmacological stress (31%). CD34+ and CD34+/chemokine (C-X-C motif) receptor 4 PCs were enumerated by flow cytometry. Change in PC count was compared between patients with and without myocardial ischemia using linear regression models. Vascular endothelial growth factor and stromal-derived factor-1α were quantified. Mean age was 63±9 years; 76% were men. The incidence of ExMI was 31% and 41% during exercise and pharmacological stress testing, respectively. Patients with ExMI had a significant decrease in CD34+/chemokine (C-X-C motif) receptor 4 (-18%, P=0.01) after stress that was inversely correlated with the magnitude of ischemia (r=-0.19, P=0.003). In contrast, patients without ExMI had an increase in CD34+/chemokine (C-X-C motif) receptor 4 (14.7%, P=0.02), and those undergoing pharmacological stress had no change. Plasma vascular endothelial growth factor levels increased (15%, P<0.001) in all patients undergoing exercise stress testing regardless of ischemia. However, the change in stromal-derived factor-1α level correlated inversely with the change in PC counts in those with ExMI (P=0.03), suggesting a greater decrease in PCs in those with a greater change in stromal-derived factor-1α level with exercise. ConclusionsExMI is associated with a significant decrease in circulating levels of CD34+/chemokine (C-X-C motif) receptor 4 PCs, likely attributable, at least in part, to stromal-derived factor-1α-mediated homing of PCs to the ischemic myocardium. The physiologic consequences of this uptake of PCs and their therapeutic implications need further investigation.

Navigating air travel and cardiovascular concerns: Is the sky the limit?

As the population ages and our ability to care for patients with cardiac disease improves, an increasing number of passengers with cardiovascular conditions will be traveling long distances. Many have had cardiac symptoms, recent interventions, devices, or surgery. Air travel is safe for most individuals with stable cardiovascular disease. However, a thorough understanding of the physiologic changes during air travel is essential given the potential impact on cardiovascular health and the risk of complications in passengers with preexisting cardiac conditions. It is important for clinicians to be aware of the current recommendations and precautions that need to be taken before and during air travel for passengers with cardiovascular concerns.